Novel 2,4-dienamides

ABSTRACT

ALIPHATIC HYDROCARBON SUBSTITUTED DI-OLEFINIC AMIDES, INTERMEDIATES THEREFRO, SYNTHESES THEREOF, AND THE CONTROL OF INSECTS.

United States Patent 3,803,185 NOVEL 2,4-D1ENAMIDES Clive A. Henrick andJohn B. Siddall, Palo Alto, Calif., assignors to Zoecon Corporation,Palo Alto, Calif. No Drawing. Continuation-impart of abandonedapplication Ser. No. 201,191, Nov. 22, 1971, which is acontinuation-in-part of application Ser. No. 187,897, Oct. 8, 1971, nowPatent No. 3,755,411, which in turn is a continuation-in-part ofapplications Ser. No. 111,650, Feb. 1, 1971, now Patent No. 3,729,486,Ser. No. 111,702, Ser. No. 111,765, Ser. No. 111,766, and Ser. No.111,770, all Feb. 1, 1971, all now abandoned, and Ser. No. 115,725, Feb.16, 1971, now Patent No. 3,706,733. This application June 26, 1972, Ser.No.

Int. Cl. C07c 103/30 US. Cl. 260-404 36 Claims ABSTRACT OF THEDISCLOSURE Aliphatic hydrocarbon substituted di-olefinic amides,intermediates therefor, syntheses thereof, and the control of insects.

This is a continuation-in-part of application Ser. No. 201,191, filedNov. 22, 1971, now abandoned, which is, in turn a continuation-in-partof application Ser. No. 187,897, filed Oct. 8, 1971, now US. Pat.3,755,411, which is a continuation-in-part of applications Ser. No.111,650, filed Feb. 1, 1971, now US. Pat. 3,729,486, Ser. No. 111,702,filed Feb. 1, 1971, now abandoned; Ser. No. 111,765, filed Feb. 1, 1971,now abandoned; Ser. No. 111,766, filed Feb. 1, 1971, now abandoned; Ser.No. 111,770, filed Feb. 1, 1971, now abandoned; and Ser. No. 115,725,filed Feb. 16, 1971, now US. Pat -3,706,733, the entire disclosures ofwhich are incorporated by reference.

This invention relates to novel aliphatic di-olefinic compounds,aliphatic tri-olefinic compounds, intermediates therefor, synthesesthereof, and the control of insects. More particularly, the noveldi-olefinic compounds of the present invention are represented by thefollowing formula:

Z is bromo, chloro, fluoro or the group --OR in which R is hydrogen,carboxylic acyl, lower alkyl, cycloalkyl, aralkyl or aryl;

Z is hydrogen, bromo, chloro or fluoro;

each of m and n is zero or the positive integer one, two

or three;

each of R and 2 is lower alkyl;

R is alkyl;

each of R R R and R is hydrogen or lower alkyl;

and

each of R and R is hydrogen, alkyl, lower alkenyl lower alkynyl,cycloalkyl, hydroxyalkyl, alkoxyalkyl, alkylthiaalkyl, aryl or aralkyor, when taken together with the nitrogen atom to which they areattached, pyrrolidino, morpholino, piperidino, piperazino or4-a1kylpiperazino, provided that when 2' is bromo, chloro or fluoro,then Z is bromo, chloro or fluoro, respectively.

The compounds of Formula A are useful for the control of insects. Theutility of these compounds as insect control agents is believed to beattributable to their juvenile horomone activity. They are preferablyapplied to the immature insect, namely-during the embryo, larvae orpupae stage in view of their effect on metamor- 3,803,185 Patented Apr.9, 1974 phosis and otherwise cause abnormal development leading to deathor inability to reproduce. These compounds are effective control agentsfor Hemipteran, such as Lygaeidae, Miridae and Pyrrhocoridae,Lepidopteran, such as Pyralidae, Noctuidae and Gelechiidae; Coleopteran,such as Tenebrionidae, Crysomelidae and Demostirdae; Dipteran such asmosquitos, flies; Homopteran, such as aphids and other insects. Thecompounds can be applied at low dosage levels of the order of 0.001 g.to 25.0 pg. per insect. Suitable carrier substances include liquid orsolid carriers, such as water, acetone, xylene, mineral or vegetableoils, talc, vermiculite, natural and synthetic resins and silica.Treatment of insects in accordance with the present invention isaccomplished by spraying, dusting or exposing the insects to the vaporof the compounds of Formula A. Generally, a concentration of less than25% of the active compound is employed. The formulations can includeinsect attractants, emulsifying agents or wetting agents to assist inthe application and effectiveness of the active ingredient. In theapplication of the compounds, there is generally employed a mixture ofthe C2,3 trans and cis isomers.

In the description hereinafter, each of RR R R Il -R Z, Z, m and n is asdefined hereinabove, unless otherwise specified.

In another embodiment of the present invention, there is providedcompounds of the following Formula B which are useful for the control ofinsects in the same manner as the di-olefinic compounds of Formula A andwhich also serve as precursors for the preparation of the compounds ofFormula A.

The compounds of the present invention can be prepared by the reactionof an acid chloride or acid bromide of Formula C with the appropriateamine of the formula:

wherein, X is bromo or chloro, Z is as above and Z" is hydrogen, bromo,chloro, fluoro or, when taken with Z, forms a carbon-carbon bond. Thesynthesis of the acid halides of Formula C is described in applicationSer. No. 187,897, filed Oct. 8, 1971, now US. Pat. 3,755,411.

The novel amides of the present invention can be prepared also by thereaction of a carbonyl of Formula I with a carbanion of the formula [Ris lower alkyl, cycloalkyl or phenyl):

In Formula I, each of Z and Z is as defined above with the exceptionthat halogen is excluded. The carbanion is generated by treatment of thecorresponding phosphonamide with base, such as alkali metal hydride oralkali metal alkoxide.

3 The amides can be prepared also by reaction of a carbonyl of FormulaIII with a carbanion or ylid of the following formulas, respectively:

R1 R14 R: Br

I l I RC=C--(CH:)nCH1CH(CH2)mCH=C=( CH:-gN

which is rearranged to the 2,4-diene system under basic conditions suchas described in copending application Ser. No. 111,768, filed Feb. 1,1971, now US. Pat. 3,716,565.

The synthesis of the compounds of Formulas I, III and IV is described inapplication Ser. No. 187,897, filed Oct. 8, 1971, the disclosure ofwhich is incorporated by reference.

The compounds of Formula A, wherein Z is hydrogen and Z is halo, can beprepared by treating a compound of Formula B with hydrogen halide incarbon tetrachlo ride or other halogenated hydrocarbon solvents of lowdielectric constant. The compounds of Formula A, .wherein Z' is halo,can be prepared by treating a compound of Formula B with bromine,chlorine or fluorine in a halogenated hydrocarbon solvent.

The compounds of Formula A, wherein Z' is hydrogen and Z is the group-OR in which R is hydrogen, can be prepared by the addition of water tothe terminal olefinic bond of a compound of Formula B using a mercuricsalt followed by reduction of the oxymercurial intermediate in situ.Suitable mercuric salts include mercuric acetate, mercuric nitrate,mercuric trifluoroacetate, mercuric acylates and mercuric halides.Suitable reducing agents include borohydrides, hydrazine and sodiumamalgam. See Brown and Rei, J. Am. Chem. Soc. 91, 5646 (1969); Brown etal., J. Am. Chem. Soc. 89, 1522 and 1524 (1967); and Wakabayashi, J.Med. Chem. 12, 191 (January 1969). By conducting the reaction in thepresence of an alcohol (ROH), such as methanol, ethanol, isopropylalcohol, benzyl alcohol, cyclopentanol, and the like, the correspondingether is prepared. The compounds of Formula A, wherein Z is --OR inwhich R is carboxylic acyl and Z is hydrogen, can be prepared from acompound of Formula A, wherein Z is -OH and Z is hydrogen, by reactionwith a carboxylic acid chloride or bromide or carboxylic acid anhydridein pyridine or by treatment with a carboxylic acid anhydride in thepresence of sodium acetate. The reaction is generally conducted at aboutroom temperature to reflux temperature for about one to forty-eighthours, shorter reaction time being favored by temperatures above roomtemperature.

The term cycloalkyl, as used herein, refers to a cyclic alkyl group ofthree to eight carbon atoms. The term aral-kyl refers to a monovalenthydrocarbon group in which an aryl group is substituted for a hydrogenatom of an alkyl group, such as benzyl, xylyl, mesityl, phenylethyl,methylbenzyl, naphthylmethyl and naphthylethyl, containing up to twelvecarbon atoms. The term aryl, as used herein, refers to an aromatic groupof up to twelve carbon atoms. Typical aromatic groups include phenyl,naphthyl, lower alkylphenyl, such as methylphenyl, ethylphenyl,t-butylphenyl or isopropylphenyl, lower alkylthiophenyl, such asmethylthiophenyl, ethylthiophenyl and isopropylthiophenyl, loweralkoxyphenyl, such as methoxyphenyl and ethoxyphenyl, halophenyl, suchas chlorophenyl, bromophenyl, iodophenyl and fluorophenyl, nitrophenyland lower alkenylphenyl, such as vinylphenyl and allylphenyl. In thecase of substituted phenyl, the substituted such as lower alkyl, loweralkylthio, lower alkoxy, halo, nitro, lower alkenyl, carbonyl, loweralkoxycarbonyl and cyano can be in one or more positions of the phenylring, usually in the para position.

The term hydroxyalkyl, as used herein, refers to an alkoxy groupsubstituted with one hydroxy group, e.g., hydroxymethyl, p-hydroxyethyland 4-hydroxypentyl. The ,term alkoxyalkyl, as used herein, refers to analkyl group substituted with one alkoxy group, e.g., methoxymethyl,2-methoxyethyl, 4-ethoxybutyl, n-propoxyethyl and t-butoxyethyl. Theterm alkenyl, as used herein, refers to an ethylenically unsaturatedhydrocarbon group, branched or straight chain, having a chain length oftwo to twelve carbon atoms, e.g., allyl, vinyl, 3-butenyl, 2- hexenyland i-propenyl. Whenever any of the foregoing terms are modified by theword lower," the chain length of the group is not more than six carbonatoms with the exception of lower alkoxyalkyl and lower alkylthiaalkylin which event a total chain length of twelve carbon atoms is themaximum.

The term carboxylic acyl, as used herein, refers to the acyl group of acarboxylic acid, anhydride or halide. The acyl group is determined bythe particular carboxylic acid, anhydride or halide employed in theesterification. Although no upper limitation need be placed on thenumber of carbon atoms contained in the acyl group within the scope ofthe present invention, generally it contains from one to eighteen carbonatoms. Typical esters of the present invention include formate, acetate,propionate, enanthate, benzoate, trimethylacetate, trichloroacetate,trifluoroacetate, t-butylacetate, phenoxyacetate, cyclopentylpropionate,aminoacetate, fi-ehloropropionate, adamantoate, octadec-9-enoate,dichloroacetate, butyrate, pentanoate, hexanoate, phenylacetate,pmethylbenzoate, fi-phenylpropionate, 3,4-dimethylbenzoate,p-isopropylbenzoate, cyclohexylacetate, stearate, methacrylate,p-chloromethylbenzoate, p-methoxybenzoate and p-nitrobenzoate.

The term alkyl refers to a branched or straight chain saturatedaliphatic hydrocarbon of one to twelve carbon atoms. The term loweralkyl refers to an alkyl group having a chain length of one to sixcarbon atoms.

The term lower alkynyl, as used herein, refers to an acetylenicallyunsaturated hydrocarbon group, branched or straight chain, having achain length of three to six carbon atoms, e.g., 3-butynyl, 2-propynyl,3-pentynyl.

The presence of an olefinic bond at position C-2 and C4 of the compoundsof Formula A give rise to four isomers, each of which is embraced by thepresent invention. The presence of three olefinic bonds in compounds ofFormula B give rise to eight isomers, each of which is embraced by thepresent invention. As mentioned above, a mixture of isomers is suitablyemployed for the control of insects, such as a mixture containing thetrans(2), trans(4) isomer and the cis(2), trans(4) isomer. Theconditions of the syntheses described herein and the reactants can beselected so as to favor formation of one isomer, such as the all transisomer, over the formation of other isomers. The selection ofappropriate conditions and reactants to favor formation of one isomerover another will be apparent to those of ordinary skill in the artgiving due consideration to the specific examples hereinafter. See alsoPattenden and Weedon, supra and Corey et al., supra. In the specificexamples herein after, when isomerism is not specified, it is understoodto include a mixture of isomers which, if desired, can

be separated using known separation methods. Hereafter, when only onedesignation of configuration is given, the designation refers toposition C2,3 and the configuration is taken to be trans at positionC4,5 when not otherwise specified. The use of trans/cis and cis/trans iswith reference to position C-2,3 and indicates a mixture of isomers.

The following examples are provided to illustrate the practice of thepresent invention. Temperature is given in degrees centigrade.

EXAMPLE 1 To a mixture of one g. of 3,7-dimethyloct-6-en-1-al, 1.5 g. ofdiethyl 3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate and 50 ml. ofdimethylformamide, under nitrogen, is slowly added sodium ethoxide(prepared from 200 mg. of sodium and 12 ml. of ethanol). The mixture isallowed to stand at room temperature for one hour and then is worked upwith ether. The ethereal extracts are dried, concentrated and thenchromatographed on silica plates eluting with hexane/ether to yieldethyl 3,7, 1l-trimethyldodeca-2,4,10-trienoate, which is predominantlytrans at position C2,3 and 04,5.

By using diethyl 3-methoxycarbonyl-2-methylprop-Z- enyl phosphonate andsodium methoxide, there is prepared methyl3,7,11-trimethyldodeca-2,4,IO-trienoate.

EXAMPLE 2 The process of Example 1 is repeated using each of thealdehydes under column (I) as the starting material to yield therespective ester under column (II):

EXAMPLE 3 A mixture of 1 g. of trans/cis methyl3,7,ll-trimethyldodeca-2,4,10-trienoate, 60 ml. of methanol, 0.5 g. ofpotassium hydroxide and 6 ml. of water is heated at reflux for about 8hours. The mixture is then diluted with water, neutralized and extractedwith ether. The organic phase is washed with water, dried over sodiumsulfate and evaporated to yield trans/cis3,7,11-trimethyldodeca-2,4,10-trienoic acid.

Using the foregoing procedure, the other esters of Example 2 arehydrolyzed to produce the respective free acids under column (III).

(III) 3,7,11-trimethyltrideca-2,4,IO-trienoic acid, 3,11-dimethyl-7-ethyltrideca-2,4,10-trienoic acid, 7,1l-diethyl-3-methyltrideca-2,4, IO-trienoic acid,3,8,l2-trimethyltrideca-2,4,ll-trienoic acid,3,7,lO-trimethylundeca-2,4,9-trienoic acid,3,7,IO-trimethyldodeca-Z,4,9-trienoic acid, and3,6,10-trimethylundeca-2,4,9-trienoic acid.

EXAMPLE 4 One gram of 3,7,11 trimethyltrideca-2,4,IO-trienoic acid in 30ml. of benzene and one mol of sodium hydride is stirred'about two hoursand then a slight excess of oxalyl chloride is added at about 0 andstirred for one hour.

The product is worked up by removal of solvent in vacuo and extractionwith pentane to yield 3,7,ll-trimethyltrideca-2,4,10-trienoyl chloride.

EXAMPLE 5 (A) To magnesium propynylide (15 g.) in 150 ml. of ether isslowly added 0.3 mole of 3,7-dimethyloct-6-enl-al and the mixture thenstirred overnight. Saturated aqueous ammonium chloride is added and thelayers separated. The organic phase, combined with ether backwashings ofaqueous phase, is washed with water, dried and solvent evaporated toyield 6,10-dimethyl-9-undecen- 2-yn-4-ol which can be purified bychromatography.

(B) A mixture of 18.5 g. of the alkynyl alcohol of part (A), g. oftriethylorthoacetate and 0.7 g. of propionic acid is refiuxed under aspinning band column to remove ethanol as it is formed. After theelimination of ethanol is about complete, the crude reaction product isdistilled under vacuum to yield ethyl3,7,ll-trimethyldodeca-3,4,10-trienoate. Alternatively, the crudereaction product is purified by chromatography on silica.

(C) A solution of 1.0 g. of the allenic ester of part (B) in 20 ml. ofethanol is treated with 4 ml. of aqueous 2 N sodium hydroxide and leftat room temperature for several minutes. The mixture is then poured intopentane and washed with saturated brine and separated. Evapora tion ofthe organic phase yields ethyl 3,7,11-trimethyldodeca-2,4,l0-trienoate.

EXAMPLE 6 The process of Example 5, part (A), is repeated using each ofthe aldehydes under column (I) as the starting material to yield therespective alkynyl alcohol under column (1V), each of which is reactedwith triethylorthoacetate using the process of Example 5, part (B), toprepare the respective allenic ester under column (V).

6, 10'dimethyl-9-dodecen-2-yn-4-ol 6-methyl-10-ethyl-9-dodecen-2-yn-4-ol6,10-diethyl-9-dodecen-2-yn-4-ol 7, 1 l-dimethyl- 1 0-dodecen-2-yn-4-ol6,9-dimethyl-8-decen-2-yn-4-ol 6,9-dimethyl-8-undecen-2-yn-4-ol5,9-dimethyl-8-decen-2-yn-4-o1 ethyl 3,7,1l-trimethyltrideca-3,4,IO-trienoate ethyl 3,11-dimethy1-7-ethyltrideca-3,4,10-trienoate ethyl3-methyl-7,11-diethyltrideca-3 ,4,10-trienoate ethyl3,8,12-trimethyltrideca-3,4,1l-trienoate ethyl3,7,l0-trimethylundeca-3,4,9-trienoate ethyl3,7,l0-trimethyldodeca-3,4,9-trienoate ethyl3,6,10-trimethylundeca-3,4,9-trienoate Using the process of Example 5,part (C), each of the allenic esters under column (V) is rearranged bytreatment with aqueous sodium hydroxide to produce the respectivea,[3-unsaturated ester.

EXAMPLE 7 To 126 mg. of a 57% dispersion of sodium hydride in oil isadded pentane. The pentane is removed and the sodium hydride washedseveral times with pentane. To the washed sodium hydride is added 582mg. of diethyl acetylmethylphosphonate in 5 ml. of tetrahydrofuran at 10under argon. After several minutes, the solution is transferred to asolution of 425 mg. of 3,7-dimethyloct- 6-en-1-a1 in about 4 ml. of drytetrahydrofuran under argon over a period of about 20 minutes at roomtemperature. After about two hours, water is added followed by additionof ether and the layers separated. The organic layer is washed withsaturated sodium chloride, dried over sodium sulfate and evaporated.under reduced pressure to yield 6,10-dimethylundeca-3,9-dien-2-one.

7 EXAMPLE 8 One gram of triphenylphosphineacetylmethylene and 425 mg. of3,7-dimethylnon-6-en-l-al are dissolved in 10 ml. of toluene andrefluxed under nitrogen overnight. The toluene is distilled off and theformed triphenylphosphine oxide crystallized by addition of pentane.Filtration and evaporation of the pentane gives a residue, which isfurther purified by preparation of thin-layer chromatography to yield6,10-dimethyldodeca-3,9-dien-2-one.

EXAMPLE 9 41 grams of 3,7-dimethyloct-6-en-1-al and 80 g. ofrecrystallized (ethyl acetate) triphenylphosphineacetylmethylene[Ramirex et al., J. Org. Chem. 22, 41 1957)] are refluxed in one literof dry toluene for 18 hours, under nitrogen. Most of the solvent isremoved in vacuo, 500 ml. pentane is added and the mixture filtered. Theflask and the triphenylphosphine oxide filter cake are washed severaltimes with pentane. The filtrate is concentrated under vacuum to yield6,10-dimethylundeca-3,9-dien-2- one.

EXAMPLE 10 Using the process of either Example 7, 8 or 9, each of thealdehydes under column (I) is converted into the respectivedi-unsaturated ketone under column (VI).

6,10-dimethyldodeca-3,9-dien-2-one,6-methyl-10-ethyldodeca-3,9-dien-2-one,6,10-diethyldodeca-3,9-dien-2-one,

7,1 1-dimethyldodeca-3,10-dien-2-one, 6,9-dimethyldeca-3,8-dien-2-one,6,9-dimethylundeca-3,8-dien-2-one, and 5,9-dimethyldeca-3,8-dien-2-one.

EXAMPLE 11 The carbanion of diethyl carbmethoxymethylphosphomate isreacted with 6,10-dimethylundeca-3,9-dien-2-one and each of the ketonesunder column (VI) using the procedure of either Example 1 or 7 toprepare the respective methyl esters under column (VII).

(VII) methyl 3,7,1 1-trimethy1dodeca-2,4,IO-trienoate, methyl3,7,1l-trimethyltrideca-2,4,IO-trienoate, methyl3,11-dimethyl-7-ethyltrideca-2,4,10trienoate, methyl3-methyl-7,11-diethyltrideca-2,4,IO-trienoate, methyl3,8,12-trimethyltrideca-2,4,l l-trienoate, methyl3,7,lO-trimethylundeca-2,4,9-trienoate, methyl 3,7,10trimethyldodeca-2,4,9-trienoate, and methyl3,6,10-trimethylundeca-2,4,9-trienoate.

EXAMPLE 12 EXAMPLE 13 One gram of trans N,N-diethyl3,7,11-trimethyldodeca- 2,4,10-trienamide is added to a solution ofthree equivalents of dry hydrogen fluoride in 30 ml. of drytetrahydrofuran. The mixture is allowed to stand at for 15 hours and isthen washed with water, dried and evaporated under reduced pressure toyield trans N,N-diethyl ll-fluoro-3,7,l1-trimethyldodeca-2,4 dienamide,which can be purified by chromatography.

8 EXAMPLE 14 The process of Example 12 is repeated with the exception ofusing dry hydrogen bromide in place of hydrogen chloride to yield transN,N-diethyl 11-bromo-3,7,11-trimethyldodeca-2,4-dienamide.

By treating the ll-bromide with anhydrous silver fluoride inacetonitrile under reflux conditions for about six hours, there isprepared trans N,N-diethyl 11-fluoro-3,7, 1l-trimethyldodeca-2,4-dienamide.

EXAMPLE 15 Chlorine gas is bubbled into ml. of carbon tetrachloride at 0until six equivalents is taken up. T wentyfive grams of transN,N-diethyl 3,7,11-trimethyldodeca- 2,4,l0-trienamide is added and themixture is then stirred and then allowed to stand at about 0 for 72hours. The mixture is then evaporated to yield trans N,N-diethyl 10, 11-dichloro-3,7,1 1-trimethyldodeca-2,4-dienamide, which can be purifiedby chromatography.

EXAMPLE 16 To a mixture of 5 g. of trans ethyl 3,7,11-trimethyldodeca2,4,10 trienoate in 100 ml. of fl'uorotrichloromethane is slowly addedfour equivalents of dry fluorine in about one hour at about -78. Afterstirring the mixture at this temperature for about 16 hours, theresultant mixture is evaporated and chromatographed on silica to yieldN,N-diethyl 10,11 difluoro-3,7,11-trimethyldodeca-2,4- dienamide, whichis further purified by chromatography.

By using bromine in the process of Example 15, there is prepared transN,N-diethyl 10,11-dibromo-3,7,11-trirnethyldodeca-2,4-dienamide.

EXAMPLE 17 To a mixture of 1.9 g. of mercuric acetate, 6 ml. of waterand 20 ml. of tetrahydrofuran is added 1.49 g. of trans ethyl3,7,11-trimethyldodeca-2,4,lo-trienoate slowly. After addition iscomplete, the reaction mixture is stirred for about 20 minutes. Themixture is cooled to about 0 and 6 ml. of aqueous sodium hydroxide (3molar) is added followed by 0.49 g. of sodium borohydride in aqueoussodium hydroxide (about 3 molar). The mixture is stirred for about 30minutes. The mixture is then decanted, concentrated, diluted with waterand then extracted with ether. The ethereal extract is washed withwater, dried over magnesium sulfate and the product chromatographed onsilica gives ethyl l1-hydroxy-3,7,11- trimethyldodeca-2,4-dienoate(trans).

The above process 'is repeated using each of the unsaturated estersunder column (11) to prepare the respective compound under column (X):

ethyl 1 1-hydroxy-3,7, 1 l-trimethyltrideca-2,4-dienoate,

ethyl 1 1-hydroxy-3,1 1-dimethyl-7-ethyltrideca-2,4-

dienoate,

ethyl 1 1-hydroxy-7,1 1-diethyl-3-methyltrideca-2,4-

dienoate,

ethyl 12-hydroxy-3,8,12-trimethyltrideca-2,4-dienoate,

ethyl 10-hydroxy-3,7,10-trimethylundeca-2,44?lienoate,

ethyl 10-hydroxy-3,7,10-trimethyldodeca-2,4-dienoate,

and

ethyl 10-hydroxy-3,6,10-trimethy1undeca-2,4-dienoate,

EXAMPLE 18 Each of the esters under column (VII) is used as the startingmaterial in the process of Example 17 to prepare the respective hydroxylunder column (XI):

methyl 11-hydroxy-3 ,7,1 1-trimethyldodeca2,4-dienoate,

methyl 1 1-hydroxy-3 ,7,11-trimethyltrideca-2,4-dienoate,

methyl 1 1-hyd;oxy-3,1 1-dimcthyl-7-ethyltrideca-2,4-

dienoate,

methyl 1 1;hydroxy-3-mcthyl-7,l 1-diethyltrideca-2,4-

dienoate,

methyl 12- hydroxy-3,8,12-trimethyltrideca-2,4-dienoate,

methyl 10-hydroxy-3,7,10-trimethylundeca-2,4-dienoate,

methyl 10-hydroxy-3,7,l0-trimethyldodeca-2,4-dienoate,

and

methyl 10-hydroxy3,6,10-trimethylundeca-Z,4-dienoate.

EXAMPLE 19 To a solution of 2 g. of trans ethyl3,7,ll-trimethyldodeca-2,4,l-trienoate in 20 ml. of ethanol, cooled to 0in an ice bath, is added a suspension of 2.32 g. of mercuric acetate in50 ml. of ethanol over 15 minutes. The reaction mixture is stirred fortwo hours and then, with cooling, 1.22 g. of potassium hydroxide in 20ml. of ethanol is added. Then 0.139 g. of sodium borohydride is added insmall portions and stirring continued for 30 minutes. The solution isdecanted, then concentrated to half volume, diluted with 100 ml. ofwater and extracted with ether (3X 50). The ethereal phase is washedwith water, dried over magnesium sulfate and the crude product chr0-matographed on silica using hexanezether to yield trans ethyl ll-ethoxy-3,7,l1-trimethyldodeca-2,4-dienoate.

EXAMPLE 20 A mixture of 1 g. of trans ethyl11-hydroxy-3,7,ll-trimethyldodeca-2,4-dienoate, m1. of acetic anhydrideand 0.5 g. of dry sodium acetate is refluxed for about five hours. Aftercooling, excess anhydride is removed by vacuum and the residue extractedwith ether. The ethereal extract is washed, dried over magnesium sulfateand evaporated to yield the corresponding acetate, trans ethyl 11-acetoxy-3 ,7,1 1-trimethyldodeca-2,4-dienoate.

EXAMPLE 21 A mixture of 2 g. of dry trans ethyl ll-hydroxy-3,7,11-trimethyldodeca-2,4-dienoate, 15 ml. of acetyl chloride and ml. of drypyridine under nitrogen is heated on a steam bath for about six hours.After cooling, the mixture is concentrated under vacuum and the residuetaken up in ether. The ethereal extract is washed, dried over magnesiumsulfate and evaporated to yield the corresponding acetate, trans ethyll1-acetoxy-3,7,11-trimethy1dodeca-2,4- dienoate.

The process of this example is repeated with the exception of usingtriethylamine in place of pyridine to yield the ll-acetate.

EXAMPLE 22 One gram of trans ethyl11-hydroxy-3,7,ll-trimethyldodeca-2,4-dienoate in 10 ml. of diglyme isadded dropwise to a slurry of 1 g. of sodium hydride in 10 ml. ofdiglyme under nitrogen. To this mixture is added 0.9 g. ofcyclohexylchloride. The reaction mixture is stirred at about for minutesand then quenched in ice water. The organic phase is separated andaqueous phase reextracted with ether. The organic materials are washedwith water, dried over sodium sulfate and evaporated to yield thecyclohexyl ether of trans ethyl ll-hydroxy- 3,7,ll-trimethyldodeca2,4-dienoate.

By using each of benzyl chloride and cyclopentyl chloride in theforegoing procedure, the corresponding benzyl ether and cyclopentylether is prepared.

EXAMPLE 23 By use of the procedure of Example 21, ethylll-hydroxy-3,7,11-trimethyldodeca-2,4dienoate is converted into thecorresponding ll-chloroacetate, ll-dichloroacetate andll-trichloroacetate using chloroacetyl chloride, dichloroacetyl chlorideand trichloroacetyl chloride, respectively.

The respective ll-trifluoroacetate, propionate, n-butanoate,n-pentanoate and n-hexanoate esters of ethyl 11-hydroxy-3,7,11-trimethyldodeca-2,4-dienoate are prepared according tothe process of Example 20 using trifluoroacetic anhydride, propionicanhydride, n-butyric anhydride, n-pentanoic anhydride and n-hexanoicanhydride or according to the process of Example 21 using the corresponding acid chloride.

EXAMPLE 24 A mixture of 20 ml. of dry formic acid and 2 g. of transethyl 3,7,11-trimethy1dodeca-2,4,IO-trienoate is heated at 50 for twohours and then poured onto ice cold potassium bicarbonate solution. Thereaction is worked up by extraction with ether, washing the etherealextract, drying over magnesium sulfate and evaporation to yield theformate of trans ethyl l1hydroxy3,7,11-trimethyldodeca-2,4-dienoate.

Using the above process, the formates of Formula A are prepared from thecorresponding precursor of Formula B having a terminal olefinic bond.

EXAMPLE 25 Fifteen grams of mercuric acetate in 50 ml. of dry .ethanolis added to 12 g. of trans ethyl 3,7,11-trimethyldodeca-2,4,10-trienoatein 30 m1. of dry ethanol cooled in an ice bath. The temperature isallowed to come to room temperature by standing overnight. Then themixture is cooled to 0, 10 g. of potassium hydroxide in ml. of ethanolis added followed by addition of 1.0 g. of sodium borohydride in smallportions. After about 30 minutes at 0, water is added and mixture leftat room temperature for two hours. The mixture is filtered, filtrateconcentrated and extracted with ether. The ethereal extract is washed,dried, and evaporated to yield trans ethyl 11 ethoxy 3,7,11trimethyldodeca-2,4-dienoate which is purified by distillation orchromatography.

By using methanol in the foregoing process in place of ethanol, there isprepared the respective ll-methyl ether. In the same way, each ofisopropanol, t-butanol, and n-propanol is added to the terminal doublebond to prepare:

ethyl l 1-isopropoxy-3,7,l1-trimethyldodeca-Z,4-dienoate,

ethyl 1 l-t-butoxy-3,7,1 l-trimethyldodeca-2,4-dienoate,

and

ethyl 1 1-n-propoxy-3,7,l l-trimethyldodeca-2,4-dienoate.

EXAMPLE 26 Each of the tri-unsaturated esters under col. (VII) is usedas the starting material in the process of Example 18 or 25 to yield therespective ethoxy substituted compound under col. (XII).

methyl 1 1-ethoxy-3,7,ll-trimethyldodeca-2,4-dienoate,

methyl 1 l-ethoxy-3,7, l 1-trimethyltrideca-2,4-dienoate,

methyl 1 1-ethoxy-3,11-dimethyl-7-ethyltrideca-2,4-

dienoate,

methyl 1 1-ethoxy-3-methyl-7,1 l-diethyltrideca-2,4-

dienoate,

methyl 12-ethoxy-3,8,1Z-trimethyltrideca-2,4-dienoate,

methyl 10-ethoxy-3,7,10-trimethylundeca-2,+dienoate,

methyl l0-ethoxy-3,7,IO-trimethyldodeca-2,4-dienoate,

and

methyl 10-ethoxy-3,6,10-trimethylundeca-2,4-dienoate.

EXAMPLE 27 A mixture of 1 g. of trans methyl 11-ethoxy-3,7,l1-trimethyldodeca-2,4-dienoate, 60 m1. of methanol, 0.5 g. of potassiumhydroxide and 6 ml. of water is heated at reflux for about eight hours.The mixture is then diluted with water, neutralized and extracted withether. The organic phase is washed with water, dried over sodium sulfateand evaporated to yield trans11-ethoxy-3,7,1l-trimethyldodeca-2,4-dienoic acid.

EXAMPLE 28 Using each of the esters under column ('II) as the startingmaterial in the process of either Example 19 or 25, there is preparedthe respective substituted ester under column (XIII).

ethyl 1l-ethoxy-3,7,l 1-trimethyldodeca-2,4-dienoate, ethyl 1l-ethoxy-3,7,11-trimethyltrideca-2,4-dienoate, ethyl1l-ethoxy-3,1l-dimethyl-7ethyl trideca-2,4-

dienoate,

ethyl 1 1-ethoxy-7, 1 l-diethyl-3-methyltrideca-2,4-dienoate, ethyl12ethoxy-3,8,12-trimethyltrideca-2,4-dienoate, ethyl10-ethoxy-3,7,10-trimethy1undeca-2,4-dienoate, ethyl10-ethoxy-3,7,IO-trimethyldodeca-2,4-dienoate, and ethyl10-ethoxy-3,6,lO-trimethylundeca-2,4-dienoate.

EXAMPLE 29 (A) To a mixture of 50 g. of 7-methoxy-3,7-dimethyloctan-l-al, 75 g. of diethyl 3-ethoxycarbonyl-2-methylprop-Z-enylphosphonate (49% trans), and 500 ml. of dimethylformamide, undernitrogen, at and with stirring, is slowly added 9 g. of sodium in 250ml. of ethanol. After addition is complete, the reaction is allowed tocontinue one hour at room temperature. The reaction is worked up withhexane, filtered through Florisil and filtrate evaporated to yieldtrans(2), trans(4) and cis(2), trans(4) ethyll1-methoxy-3,7,11-trimethyldodeca-2,4- dienoate (about 60% trans,trans).

(B) A mixture of 45 g. of the ethyl ester of part (A), 350 ml. ofethanol, 100 ml. of water and 70 ml. of 50% aqueous NaOH is refluxed for22 hours. Etanol is then removed under reduced pressure, water addedfollowed by extraction with ether. The aqueous phase is adjusted toabout pH 8 using aqueous HCl and 31 g. of S-benzyl-isothiouroniumhydrochloride in water is added. The thusformed salt is filtered, washedwith water, recrystallized from aqueous methanol (twice) and thentreated with aqueous I-ICl/ ether and worked up to yield 11-methoxy-3,7,11-trimethyldodeca2,4-dienoic acid which crystallizes on cooling.

(C) Theacid (0.5 g.) of part (B) is methylated using diazomethane inether, followed by chromatography on prep. TLC and distillation (shortpath) to prepare' methyl ll-methoxy 3,7,1l-trimethyldodeca-2,4-dienoate[95.2% trans(2), trans(4)]. In the same way, using diazoethane isprepared ethyl 1l-methoxy-3,7,1l-trimethyldodeca-2,4- dienoate [95.2%trans(2), trans(4)].

EPMMPLE 30 To 0.5 g. of the acid of Etample 33 in ml. of benzene, undernitrogen, is added 0.055 g. of sodium hydride. After stirring at roomtemperature for minutes, 0.17 ml. of oxalyl chloride is added followedby stirring for 2.5 hours. Then 2 ml. of isopropanol is added. Afterabout 3 hours, the reaction is worked up by extraction with ether,washing with sodium bicarbonate and brine, dry ing over calcium sulfateand isolation to yield isopropyl l1 methoxy 3,7,11 trimethyldodeca 2,4dienoate (about 91% trans, trans).

EXAMPLE 31 Sodium etoxide (prepared from 0.2 g. of sodium and 12 ml. ofethanol] is slowly added to a mixture of 1.1 g. of7-ethoxy-3,7-dimethyloctan 1-al, diethyl3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate and 50 ml. ofdimethylformamide, with stirring under nitrogen, at 0". The reaction isstirred for 1.5 hours after addition is complete and then worked up byextraction with ether to yield 11-ethoxy-3,7,11-trimethyldodeca-2,4-dienoate, mostly trans- (2), trans(4),which can be further purified by chromatography or distillation.

EXAMPLE 32 A mixture of 5 g. of hydroxycitronellal (7-hydroxy-3,7-dimethyloctan-l-al), 8.5 g. of di-isopropyl3-ethoxycarbonyl-2-methylprop-2-enyl phosphonate and 40 ml. ofdimethylformamide, under nitrogen and cooled in an icebath, is stirredfor 0.5 hour and then ground NaOI-I (1.165 g.) is added. The reactionmixture is stirred at room temperature for three hours and thenhexane/water (1: 1) added. The organic layer is washed with water andbrine, dried over calcium sulfate and concentrated. The concentrate isfiltered through Florisil using hexane and hexane/ether. The filtrate isconcentrated and then distilled to yield ethylll-hydr0xy-3,7,ll-trimethyldodeca-Z, 4-dienoate (about trans-2-trans-4).

EXAMPLE 3 3 To 40 ml. of ice cold ethanol is added 2.49 g. of acetylchloride. The resulting solution is stirred at 0 for 15 minutes and 1.0g. of trans N,N-diethyl 3,7,ll-trimethyldodeca-2,4,l0-trienamide added.The solution is stirred for one hour at 0 and for 48 hours at 25.Solvent is removed under reduced pressure and the concentrate taken upin hexane. The hexane solution is washed with water until the aqueouswash is neutral and then with brine. The solution is dried over calciumsulfate and solvent evaporated to yield trans N,N-diethyl 11-chloro-3,7,1 1-trimethyldodeca-2,4-dienamide.

EXAMPLE 34 (A) grams of 3,7-dimethyloct-6-en-l-ol is dissolved in ml. ofpyridine and 100 ml. of acetic anhydride and left at room temperaturefor about 48 hours. Then the mixture is extracted with ether and theethereal extracts washed with water, 10% aqueous HCl and brine to yieldl-acetoxy-3,7-dimethyloct-6-ene, which is purified by distillation.

(B) 150 grams of mercuric acetate in 400 ml. of dry ethanol is added to100 g. of l-acetoxy-3,7-dimethyloct-6- ene (citronellol acetate) in 200ml. of dry ethanol cooled in an ice-bath. The temperature is allowed tocome to room temperature by standing overnight. Then the mixture iscooled to 0, 100 g. of potassium hydroxide in 1.5 l. of ethanol is addedfollowed by addition of 10 g. of sodium borohydride in small portions.After about 30 minutes at 0, water (100 ml.) is added and the mixtureleft at room temperature for two hours. The mixture is filtered,filtrate concentrated and extracted with ether. The ethereal extract iswashed, dried and evaporated to yield 7-ethoxy-3,7-dimethyloctan-l-olwhich is purified by distillation or chromatography.

By using methanol in the foregoing process in place of ethanol, there isobtained 7-meth0xy-3,7-dimethyloctan-l-ol.

(C) A mixture of 1.9 of 7-ethoxy-3,7-dimethyloctan-1- 01 and 10 ml. ofpyridine is added to a suspension of 8.0 g. of chromium trioxide in 100ml. of pyridine with stirring under nitrogen. After about 4 hours atroom temperature, the reaction is poured into saturated sodiumbicarbonate and worked up with ether followed by washing with 2 N NaOH,water, 10% HCl, water and brine and evaporated under reduced pressure todryness and then filtered with hexane to yield7-ethoxy-3,7-dimethyloctanl-al.

(D) A mixture of 9.0 g. of 7-ethoxy-3,7-dimethyloctanl-al and 15 g. oftriphenylphosphineacetylmethylene in EXAMPLE 35 Each of the aldehydesunder col. (XIV) is reacted with the carbanion of di-isopropyl3-isopropoxycarbonyl-2- methylprop-Z-enyl phosphonate using theprocedure of Example 32 to prepare the respective isopropyl ester undercol. (XV).

13 (XIV) 3,6,7-trimet'hyloct-6-en-l-al, 3,6,7-trimethylnon-6-en-q -al,2,5dimethylhex-4-en-l-al, 2,4,5-trimethyl-4-en-l-al,3,5,6'trimethylhept-5-en-l-al, 2,5,6-trimethylhept-5-en-l-al,3,8-dimethylnon-7-en-1-a1, and 3,-9edimethyldec-8-en-l-al.

isopropyl 3,7,10, l 1-tetramethyldodeca-2,4, 1 O-trienoate, isopropyl3,7,10,-l l-tetramethyltrideca-2,4, lO-trienoate, isopropyl3,6,9-trimethyldeca-2,4-S-trienoate,

isopropyl 3,6,8,9-trimethyldeca2,4,8-trienoate, isopropyl3,7,9,l0-tetramethylundeca-2,4,9-trienoate, isopropyl3,6,9,10-tetrarnethylundeca-2,4,9-trienoate, isoproply3,7,12-trimethyltrideca-2,4,ll-trienoate, and isopropyl3,7,13-trimethyltetradeca-2,4,l2-trienoate.

The reaction of the aldehydes under col. (XIV) with the carbanion ofdiethyl 3-methoxycarbonyl-Z-methylprop-Z-enylphosphonate yields therespective methyl triunsaturated esters. In the same way the respectiveethyl tri-unsaturated esters are prepared using diethyl3-ethoxycarbonyl-2-methylprop-Z-eriylphosphonate.

Following the procedure of Example 19 or 25, methanol is added to theterminal double bond of each of the esters under col. (XV) to prepare:

isopropyl lll-methoxy-3,7,l0,ll-tetramethyldodeca-2,4-

dienoate,

isopropyl 1 l-methoxy-3,7, 10, l l-tetramethyltrideca-2,4-

dienoate,

isopropyl 9-methoxy-3,6,9-trimethyldeca-2,4-dienoate,

isopropyl 9-methox'y-3,6,8,9-tetramethyldecan-2,4- dienoate,

isopropyl 10methoxy-3,7,9,10-tetramethylundeca-2,4-

dienoate,

isopropyl l0-methoxy-3,6,9,l0-tetramethylundeca-2,4-

dienoate,

isopropyl 12-methoxy-3,7,l2-trimethyltrideca-2,4-

dienoate, and

isopropyl l3-methoxy-3,7,l3-trimethyltetradeca-2,4-

dienoate.

In the same way, ethanol is added to the terminal double bond to preparethe respective ethoxy substituted 2,4- dienoates. Using the procedure ofExample 17, water is added to the terminal double bond to prepare therespective hydroxy-substituted 2,4dienoate.

EXAMPLE 36 (A) Eighty ml. of a 3 M solution of methylmagnesium bromidein ether is added slowly to 31 g. of citronellal in 250 ml. of dryether. The mixture is heated at reflux for about one hour, cooled to 0and treated with saturated aqueous ammonium chloride until reactionsubsides. The

. organic layer is separated and the aqueous layer extracted with ether.The organic layer and ether extracts are combined, washed with water andbrine and dried over magnesium sulfate. Evaporation of the solvent gives4,8-dimethylnon-7-en-2-ol.

(B) A solution of 47 g. of 4,8-dimethylnon-7-en-2-ol in 250 ml. ofmethylene chloride is cooled to about 10 as a solution of 46.4 g. ofsodium dichromate in 125 ml. of water is added. The mixture ismaintained at about 10 as a solution of 46.3 g. of sulfuric acid in 100ml. of water is added over about 45 minutes. The mixture is allowed toattain room temperature and, after about 3 hours, the organic layer isseparated and the aqueous layer is extracted with methylene chloride.The combined organic materials are washed with saturated potassium 14bicarbonate, water and saturated sodium chloride, dried over magnesiumsulfate and evaporated to yield 4,8-dimethylnon-7-en-2-one.

The Grignard reaction of part (A) is repeated using each3,7-dimethylnon-6-en-l-al, 3-methyl-7-ethylnon-6-enl-al,3,6,7-trimethyloct-6-enl-al, 3,7,8-trimethylnon-7-enl-al,2,4,5-trimethylhex-4-en-l-al, 2,5-dimethylhex-4-enl-al,3,5,6-trimethylhept-5-en-l-al, 3,6-dimethylhept-5-enl-al,2,6-dimethylhept-5-en-1-al and 2,5,6-trimethylhept- S-en-l-al in placeof citronellal to yield the respective secondary alcohol-4,8-dimethyldec-7-en-2-ol, 4-methyl-8-ethyldec-7-en-2-ol,4,7,8-trimethylnon-7-en-2-ol, 4,8,9-trimetliyldec-8-en-2-ol,3,5,6-trimethylhept-5-en-2-ol, 3,6-dimethylhept-5-en-2-ol,

4, 6,7-trimethyloct-6-en-2-ol, 4,7-dimethyloct-6-en-2-ol,3,7-dimethyloct-6-en-2-ol, and 3,6,7-trimethyloct-6-en-2-ol.

Each of the above alcohols is oxidized to prepare the respective ketone4,8-dimethyldec-7-en-2-one, 4-methyl-8-ethyldec-7-en-2-one,4,7,8-trirnethylnon-7-en-2-one, 4,8,9-trimethyldec-8-en-2-one, 3,5,6-trimethylhept-5 -en-2-one, 3,6-dimethylhept-5-en-2-one,4,6,7-trimethyloct-6-en-2-one, 4,7-dimethyloct-6-en-2-one,3,7-dimethyloct-6-en-2-one, and 3,6,7-trimethyloct 6-en-2-one.

(C) Each of the ketones of part (B) is reacted with the carbanion ofdiethyl 3-ethoxycarbonyl-Z-methylprop- 2-enyl phosphonate according toprocedures described above to prepare the respective tri-unsaturatedester, i.e.-

ethyl 3,5,7 11-tetramethyldodeca-2,4,IO-trienoate, ethyl 3,5 ,7,11-tetramethyltrideca-2,4, IO-trienoate, ethyl3,5,7-trimethyl-ll-ethyltrideca-ZA,IO-trienoate, ethyl3,5,7,10,l1-pentamethyldodeca-2,4, 10-trienoate, ethyl3,5,7,1l,l2-pentamethyltrideca-2,4,l l-trienoate, ethyl3,5,6,8,9-pentamethyldeca-2,4,S-trienoate, ethyl3,5,6,9-tetramethyldeca-2,4,8-trienoate,

ethyl 3,5,7,9,l0-pentamethylundeca-2,4,9-trienoate, ethyl3,5,7,|10-tetramethylundeca-2,4-9-trienoate, ethyl3,5,6,lO-tetramethylundeca-2,4,9-trienoate, and ethyl3,5,6,9,l0-pentamethylundeca-2,4,9-trienoate.

EXAMPLE 37 (A) Each of the ketones of part (B) of Example 36 is reactedwith the carbanion of diethyl 3-ethoxycarbonyl-1,Z-dimethylprop-Z-enylphosphonate to prepare the respective trienoate,i.e.-

ethyl 3,4,5,7,1l-pentamethyldodeca-2,4,10-trienoate,

ethyl 3,4,5,7,l1-pentamethyltrideca-2,4,lO-trienoate,

ethyl 3,4,5,7-tetramethyl-l1-ethyltrideca2,4,10-

trienoate,

ethyl 3,4,5,7,10,11-hexamethyldodeca-2,4,IO-trienoate,

ethyl 3,4,5 ,1 1,12-hexamethyltrideca-2,4,ll-trienoate,

ethyl 3,4,6,8,9-hexamethyldeca-2,4,8-trienoate,

ethyl 3,4,5,6,Q-pentamethyldeca-2,4,8-trienoate,

ethyl 3,4,5,7,9,1O heXamethylundeca-Z,4,9-trienoate,

ethyl 3,4,5,7,10-pentamethylundeca-2,4,9-trienoate,

ethyl 3,4,5,6,lO-pentamethylundeca-2,4,9-trienoate, and

ethyl 3,4,5,6,9,lO-hexamethylundeca-2,4,9-trienoate.

(B) Each of the aldehydes under col. (I) is reacted with the carbanionof diethyl 3-ethoxycarbonyl-l,2-dimethylprop-Z-enyl phosphonate toprepare the respective trienoate, i.e.

ethyl 3,4,7,1l-tetramethyltrideca-2,4,lO-trienoate, ethyl3,4,11trimethyl-7-ethyltrideca-2,4,IO-trienoate, ethyl 3,4-dimethyl-7,ll-diethyltrideca2,4,10-trienoate, ethyl 3,4,8,l2-tetramethyltrideca-2,4, 1 l-trienoate, ethyl3,4,7,lO-tetramethylundeca-Z,4,9-trienoate,

ethyl 3,4,7,10-tetramethyldodeca-2,4,9-trienoate, and ethyl3,4,6,10-tetramethylundeca-2,4,9-trienoate.

By use of the procedure of part B of this example, other aldehydes ofFormula I (R is hydrogen are converted into the respective ester ofFormula B wherein R is hydrogen and R is methyl or other lower alkyl.Similarly following the procedure of part (A) of this example, otherketones of Formula I (R is lower alkyl) are cOnverted into esters ofFormula B, wherein each of R and R is lower alkyl. Using the process ofpart (C) of Example 36 other esters of the present invention of FormulaB, wherein R is hydrogen and R is methyl or other lower alkyl, can beprepared using a ketone of Formula I (R is lower alkyl) as theprecursor.

(C) Each of the esters of this example and Example 36 can be hydrolyzedto the free acid according to the procedure of Example 3 or 29.

EXAMPLE 38 Methanol is added to the terminal bond of ethyl 3,4,7,11-tetramethyldodeca-2,4,lo-trienoate using the process of Example 19 or25 to give ethyl ll-methXy-3,4,7,'lltetramethyldodeca-2,4-dienoate. Inthe same manner, water is added to give ethylll-hydroxy-3,4,7,ll-tetramethyldodeca-2,4-dienoate. Similarly, there isprepared ethyl ll-methoxy 3,5,7,11-tetramethyldodeca-2,4-dienoate andethyl ll-hydroxy 3,5,7,l1-tetramethyldodeca-2,4-dienoate from ethyl3,5,7,11-tetramethyldodeca-2,4,10-trienoate.

EXAMPLE 39 (A) To a solution of 1.8 g. of 6,10-dimethylundeca-3,9-dien-2-one in 20 ml. of ethanol, cooled to 0 by an ice bath is addeda suspension of 2.32 g. of mercuric acetate in 50 ml. of ethanol overminutes. The reaction mixture is stirred for two hours and then, withcooling, to 1.22 g. of potassium hydroxide in 20 mL of ethanol is added.Then 0.139 g. of sodium borohydride is added in small portions andstirring continued for 30 minutes at -20. The solution is decanted, thenconcentrated to half volume, diluted with 100 ml. of water and extractedwith ether (3X 50). The ethereal phase is washed with water, dried overmagnesium sulfate and the crude product chromatographed on silica toyield 10- ethoxy-6,10-dimethylundec-3-en-2-one.

The process of this example is repeated using each of the compoundsunder column (VI) as the starting material to prepare the respectiveethoxy substituted compound column (XVI).

10-ethoxy-6,10-dimethyldodec-3-en-2-one,10-ethoxy-6-methyl-l0-ethyldodec-3-en-2-one,l0-ethoxy-6,10-diethyldodec-3-en-2-one,

1 l-ethoxy-7, l l-dimethyldodec-3-en-2-one,9-ethoxy-6,9-dimethyldec-3-en-2-one,9-ethoxy-6,9-dimethylundec-3-en-2-one, and9-ethoxy-5,9-dimethyldec-3-en-2-one.

Following the process of Example 11, l0-ethoxy-6,l0-dimethylundec-B-en-Z-one is converted into methyl 11-ethoxy-3,7,ll-trimethyldodeca-2,4-dienoate. Reaction of10-ethoxy-6,l0-dimethylundec-3-en-2-one with the carbanion of diethylcarboethoxymethylphosphonate yields ethyl 1 1-ethoxy-3 ,7, 1l-trimethyldodeca-2,4-dienoate.

By using other alcohols in the process of this example in lieu ofethanol, such as methanol, etc., the respective ethers are obtained,e.g. 10-methoxy-6,lO-dimethylundec- 3-eu-2-one.

(B) The process of part (A) is repeated using the starting material3,7-dimethyloct-6-en-l-al and each of the aldehydes under column (I) orthe acetal thereof to prepare the respective compounds under column(XVII).

(XVII) 7-ethoxy-3,7-dimethyloctan-l-al, 7-ethoxy-3,7-dimethylnonanl-al,7-ethoxy-3-ethyl-7-methylnonan-l-al, 7 -ethoxy-3,7-diethylnonl-al,8-ethoxy-4,8-dimethylnonan-l-al, 6-ethoxy-3,6-dimethylheptan-l-al,6-ethoxy-3,6-dimethyloctan-l-al, and 6-ethoxy-2,6-dimethylheptan-l-al.

Using 7-ethoxy-3,7-dimethyloctan-l-al as the starting material in theprocess of either Example 7, 8 or 9, there is prepared10-ethoxy-6,l0-dimethylundec-3-en-2- one.

EXAMPLE 40 Two grams of 3,7,1l-trimethyltrideca-2,4,IO-trienoic acidchloride is added to 50 ml. of benzene, cooled to 0 and saturated withammonia under nitrogen. The mixture is allowed to stand for about onehour and then it is washed with water, dried over sodium sulfate andevaporated to yield 3,7,11-trimethyltrideca-2,4,IO-trienamide.

EXAMPLE 41 Three grams of 3,7,11-trimethyld0deca-2,4,lO-trienoylchloride in benzene is mixed with 2.5 g. of diethylamine in benzene andthe resulting mixture allowed to stand at room temperature for about twohours. The mixture is concentrated under reduced pressure and theresidue taken up in benzene, washed with dilute aqueous sodiumbicarbonate and water, dried over sodium sulfate and evaporated to yieldN,N-diethyl 3,7,ll-trimethy1dodeca- 2,4,l0-trienamide.

By use of the foregoing procedure, each of dimethylamine, ethylamine,pyrrolidine, piperidine, aniline, morpholine and 2-methoxyethylamine isreacted with the acid chloride to yield the corresponding amide, thatis, N,N- dimethyl 3,7,11 trimethyldodeca 2,4,10 trienamide, N-ethyl3,7,1l-trirnethyldodeca-2,4,IO-trienamide, etc.

EXAMPLE 42 Two grams of 3,7,11-trimethyltrideca-2,4,IO-trienoyl chlorideis added to a solution of 2 g. of 4-ethylpiperazine and 20 ml. oftetrahydrofuran. The mixture is allowed to stand for four hours at 0,then 50 ml. of benzene is added and the resulting mixture washed withwater, dried over sodium sulfate and evaporated to yieldN-(4'-ethylpiperazino)-3,7,l1-trimethyltrideca-2,4,IO-trienamide.

EXAMPLE 43 Following the process of Example 41, the acid chloride ofeach of the acids under column (111) is reacted with diethylamine toprepare the respective amide:

N,'N-diethyl 3,7,1l-trimethyltrideca-2,4,Ill-trienamide,

N,N-diethyl 3,11-dimethyl-7-ethyltrideca-2,4,lO-

trienamide,

N,l\'-diethyl 3-methyl-7,11-diethyltrideca-2,4,l0-

trienamide,

N,N-diethyl 3,8,12-trimethyltrideca-2,4,ll-trienamide,

N,N-diethyl 3,7,10-trimethylundeca-2,4,9-trienamide,

N,N-diethyl 3,7,10-trimethyldodeca-2,4,9-trienamide, and

N,N-diethyl 3,6,lO-trimethylundeca-2,4,9-trienamide.

EXAMPLE 44 The process of Example 1 is repeated with the exception ofusing diethyl 3-(N,N-diethylcarbonyl)-2-methylprop- 2-enylphosphonan'iide in place of the phosphonate to yield N,N-diethyl3,7,11-trimethyldodeca-2,4,IO-trienamide.

17 EXAMPLE 45 Sodium hydride (1.7 g., 57% in oil) is washed three timeswith dry hexane. The hexane is removed and 15 ml. of dry tetrahydrofuranis added. N,N-diethyl diethoxyphosphonoacetamide (0.9 g.), dissolved in5 ml. of dry tetrahydrofuran, is added and stirred for about 40 minutesThen about 0.7 g. of 6,10-dimethyldodeca-3,9-dien- 2-one in 5 ml. of drytetrahydrofuran is added with stirring and cooling with an ice-bath. Theice-bath is removed after addition is completed and stirring continuedfor about two hours. Then the mixture is poured into water and extractedwith ether. The ether extracts are combined, washed with water, driedover magnesium sulfate and evaporated under reduced pressure to yieldcis/ trans N,N-diethyl 3,7,11-trimethyltrideca-2,4,lO-trienamide.

EXAMPLE 46 The procedure of Example 12 or 33 is repeated usingN,N-diethyl 3,7,1l-trimethyldodeca-2,4,IO-trienamide and the amides ofExample 43 to prepare:

N,N-diethyl l'1-chloro-3,7,1 l-trimethyldodeca- 2,4-dienamide,

N,N-diethyl 1 1-chloro-3,7,1 l-trimethyltrideca- 2,4-dienamide,

N,N-diethyl 1 1-chloro-3,l1-dimethyl-7-ethyltrideca- 2,4-dienamide,

N,N-diethyl 1 1-chloro-3 -methyl-7,1 l-diethyltrideca- 2,4-dienamide,

N,N-diethyl 12-chloro-3,8,12-trimethyltrideca- 2,4-dienamide,

N,N-diethyl -chloro-3,7,IO-trimethylundeca- 2,4-dienamide,

N,N-diethyl 10-chloro-3,7,IO-trimethyldodeca- 2,4-dienamide,

N,N-diethyl 10-chloro-3,6, IO-trimethylundeca- '5 2,4dienamide.

.Each of N,N-dimethyl 3,7,1l-trimethyltrideca-2,4,10- trienamide,N-methyl 3,7,1Hrimethyltrideca-ZA,IO-trienamide, N,N-isopropyl3,7,11-trimethyltrideca-2,4,IO-trienamide, N ethyl3,7,11-trimethyldodeca-2,4,IO-trienamide and N,N-di-n-butyl3,7,11-trimethyldodeca-2,4,10- trienamide is used as the startingmaterial in the process of Example 12 or 33 to prepare the respectivecompound, that isN,N-dim'ethyl 11-chloro-3,7,1l-trimethyltrideca-2,4-dienamide, N-methyl 11-chloro-3,7,1l-trimethyltrideca-2,4-dienamide,N,N-isopropyl 11-chloro-3,7,11-trimethyltrideca-2,4-dienamide, N-ethyl11-chloro-3,7,11- trimethyldodeca-2,4-dienamide and N,N-di-n-butyl 11-chloro-3,7,l 1-trimethyldodeca-2,4-dienamide.

Using the procedure of Examples 15 and 16, each of trans N,N-diethyl10,1l-dichloro-3,7,1l-trimethyldodeca- 2,4-dienamide, trans N,N-diethyl10,11-difluoro-3,7,11-trimethyldodeca-2,4-dienamide and transN,N-diethyl 10,11- dibromo 3,7,11 trimethyldodeca-2,4-dienamide isprepared from trans N,N-diethyl 3,7,l1-trimethyldodeca-2,4,10-trienamide.

Following the procedure of Examples 13 and 14, each of N,N-diethyl1l-fluoro-3,7,l1-trimethyldodeca-2,4-dienamide and N,N-diethylll-bromo-3,7,1l-trimethyldodeca- 2,4-dienamide is prepared fromN,N-diethyl 3,7,l1-trimethyldodeca-2,4, lo-trienamide.

EXAMPLE 47 The procedure of Example 17 is utilized for the addition ofwater to the terminal double bond of N,N-diethyl3,7,11-trimethyldodeca-2,4,IO-trienamide and each of the amides ofExample 43 to prepare:

N,N-diethyl l1- hydroxy-3,7,11-trimethyldodeca-2,4-

dienamide,

N,N-diethyl ll-hydroxy-3,7,1 1-trimethyltrideca-2,4-

dienamide,

N,N-diethyl ll-hydroxy-3,l l-dimethyl-7-ethyltrideca-2,4-dienamide,

N,N-diethyl 1 1-hydr0xy-3-methyl-7,1 l-diethyltrideca-2,4-dienamide,

N,N-diethyl 12-hydroxy-3,8,IZ-trimethyltrideca- 2,4-dienamide,

N,N-diethyl 10-hydroxy-3,7,IO-trimethylundeca- 2,4-dienamide,

N,N-diethyl 10-hydroxy-3,7,lO-trimethyldodeca- 2,4-dienamide, and

N,N-diethyl l0-hydroxy-3,6,IO-trimethylundeca- 2,4-dienamide.

Each of N,N-dimethyl 3,7,1l-trimethyltrideca-2,4,l0- trienamide,N-methyl 3,7,11 trimethyltrideca 2,4,10- trienamide, N,N-isopropyl3,7,11 trimethyltrideca-2,4,l0- trienamide, N-ethyl 3,7,11trimethyldodeca 2,4,10 trienamide and N,N-di-n-butyl 3,7,11trimethyldodeca-2,4, 10 trienamide is used as the starting material inthe process of Example 17 to prepare the respective hydroxyl, that isN,Ndimethyl 11- hydroxy 3,7,11 trimethyltrideca 2,4 dienamide, N-methyl11-hydroxy-3,7,11-trimethyltrideca 2,4 dienamide, N,N-isopropyl l1hydroxy 3,7,11 trimethyltrideca 2,4 dienamide, N- ethyl 11 hydroxy3,7,11 trimethyldodeca 2,4 dienamide and N,N-di-n-butyl11-hydroxy-3,7,ll-trimethyldodeca-2,4-dienamide.

Following the procedure of Example 19 or 25, ethanol is added to theterminal bond of N,N-diethyl 3,7,11-trimethyldodeca 2,4,10 trienamideand each of the amides of Example 43 to prepare:

N,N-diethyl 1 1-ethoxy-3,7,1l-trimethyldodeca- 2,4-dienamide,

N,N-diethyl 1 1-ethoxy-3,7,l l-trimethyltrideca- 2,4-dienamide,

N,N-diethyl 11-ethoxy-3,1 1-dimethyl-7-ethyltrideca- 2,4-dienamide,

N,N-diethyl 1 l-ethoxy-3-methyl-7, 1 l-diethyltrideca- 2,4-dienamide,

N,N-diethyl l2ethoxy-3,8,12-trimethyltrideca- 2,4-dienamide,

N,N-diethyl 10-ethoxy-3,7,IO-trimethyltrideca- 2,4-dienamide,

N,N-diethyl 10-ethoxy-3,7,IO-trimethyldodeca- 2,4-dienamide,

N,N-diethyl 10-ethoxy-3,6,10-trimethylundeca- 2,4-dienamide.

The respective methoxy 2,4 dienamides are prepared by repeating theabove process and using methanol in place of ethanol. Thus, there isprepared N,N-diethyl 11- methoxy 3,7,11 trimethyldodeca 2,4 dienamide,N- ethyl l1 methoxy-3,7,11-trimethyldodeca-2,4-dienamide, etc.

Each of the acid chlorides,

1 1-methoxy-3,7,1 l-trimethyldodeca-2,4-dienoyl chloride,

10-methoxy-3,7, 10-trimethylundeca-2,4-dienoyl chloride,

1 1-methoxy-3 ,7,1 1-trimethyltrideca-2,4-dienoyl chloride,

1 1-methoxy-3,7, 10,1 1-tetramethyldodeca-2,4-dienoyl chloride,

1 1-methoxy-3 1 1-dimethyl-7-ethyltrideca-2,4-dienoyl chloride,

11-methoxy-3,5,7,l1-tetramethyldodeca-2,4-dienoyl chloride,

1 1-meth0xy-3,4,7,1 1-tetramethyldodeca-2,4-dienoyl chloride, and

11-methoxy-3,5,7,10,1 l-pentamethyldodeca-2,4-

dienoyl chloride 19 is reacted with ethylamine using the procedure ofExample 41 to prepare the respective amide, 1.e.,

N-ethyl 1 l-methoxy-3,7,1l-trimethyldodeca- 2,4-dienamide,

N-ethyl l-methoxy-3,7,l0-trimethylundeca- 2,4-dienamide,

N-ethyl 1 1-methoxy-3,7, l l-trimethyltrideca- 2,4-dienamide,

N-ethyl l1-methoxy-3,7,l0, 1 l-tetramethyldodeca- 2,4-dienamide,

N-ethyl 1 1-methoxy-3,l1-dimethyl-7-ethyltrideea- 2,4-dienamide,

N-ethyl ll-methoxy-3,5,7,1 l-tetramethyldodeca- 2,4-dienamide,

N-ethyl 1 l-methoxy-3,4,7,1 l-tetramethyldodeca- 2,4-dienamide, and

N-ethyl l 1-methoxy-3,5,7, 10,1 l-pentamethyldodeca- 2,4-dienamide.

The reaction of 11-hydroxy-3,7,ll-trimethyldodeca-2,4- dienoyl chloridewith ethylamine affords N-ethyl ll-hydroxy-3,7,1l-trimethyldodeca-2,4-dienamide.

By use of the foregoing procedure, each of dimethylamine,isopropylamine, methylethylamine, pyrrolidine, piperidine, aniline,morpholine and Z-methoxyethylamine is reacted with ll-methoxy 3,7,11trimethyldodeca-2,4- dienoyl chloride to yield the corresponding amide,that N-isobutyl 1l-methoxy-3,7,1l-trimethyldodeca- 2,4-dienamide,

N-isopropyl 1l-methoxy-3,7,l l-trimethyldodeca- 2,4-dienamide,

N-methyl-N-ethyl l 1-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienamide,

pyrrolidino 1 l-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienamide,

piperidino l l-methoxy-3,7,l l-trimethyldodeca- 2,4-dienamide,

N-phenyl l l-methoxy-3,7,1 l-trimethyldodeca- 2,4-dienamide,

morpholino l 1-methoxy-3 ,7,1 l-trimethyldodeca- 2,4-dienamide, and

N-(2'-methoxyethyl) l 1-methoxy-3,7,1 l-trimethyldodeca-2,4-dienamide.

EXAMPLE 48 Each of s butylamine, isobutylamine, t butylamine,methylisopropylamine, ethyl n propylamine, cyclohexylamine, allylamine,methallylamine, ethenylamine, 2-hydr'oxypropylamine and benzylamine isreacted with 11- methoxy 3,7,11 trimethyldodeca 2,4 dienoyl chloride toprepare the respective amide, that is 20 EXAMPLE 49 To a solution of6.14 g. of ll-methoxy-3,7,1l-trimethyldodeca-2,4-dienoic acid and drybenzene, under nitrogen, is added 7.7 ml. of oxalyl chloride. Thereaction is stirred for two hours at room temperature and then solventremoved under reduced pressure. Then 8 ml. of diethylamine in chilleddry benzene is added. The mixture is allowed to come to room temperatureand then is stirred for 1.5 hours. The mixture is washed with dilutehydrochloric acid, water and brine and ether added followed by dryingover calcium sulfate and solvent evaporated to yield N,N-diethyl 11methoxy 3,7,11 trimethyldodeca- 2,4-dienamide, which can be purified bypreparative thinlayer chromatography using ethyl acetate/hexane.

The process of this example is repeated using ethylamine in place ofdiethylamine to prepare N-ethyl 11- methoxy-3,7,11-trimethyldodeca-2,4-dienamide.

The process of this example is repeated using isopropylamine in place ofdiethylamine to prepare N-isopropyl 1 l-methoxy-3,7,l1-trimethyldodeca-2,4-dienamide.

Three groups of 30 each of Aedes aegypti, fourth instar larvae, in 50ml. of tap water containing a few drops of liver powder suspension, roomtemperature of 28 and photoperiod of 18 hours, are treated with N ethylll-methoxy-3,7,ll trimethyldodeca-2,4-dienamide (about 73% trans,trans)using 50 microliters of acetone as the carrier at three difierent dosagelevels. A fourth group is maintained under identical conditions. Eachgroup is scored after seven days by the following system: 0=normaladult, completly emerged (free or floating); 1=abnormal adult,non-viable; 2=incompletely emerged adult; 3=dead pupa; and 4=deadlarvae. For each group, the total number of animals in classes 1-4 isdivided by 30 to determine the percentage result. The ID is computed byplotting on semi-logarithmic paper, the dose on the horizontal axis andthe percentage response on the 'verticle axis. The ID was determined tobe less than 0.1 ppm. Each of the larvae of the control group developedinto normal adults.

Three groups of 20 each of Tenebrio molitor pupae- (less than 24 hoursold) maintained on wheat germ and bran, 25 room temperature, 18 hourslight, are treated at 0.01, 0.1 and 1.0 g. with N,N-diethyl11-methoxy-3,7, l1-trimethyldodeca-2,4-dienamide (approximately 52%trans,trans) using acetone carrier. The active agent is placed on the5th abdominal sternite using a syringe. The ID was less than 0.001 g.

A fine dust is prepared of 10 parts of N,N-diethyl 1l-methoxy-3,7,ll-trimethyldodeca-2,4-dienamide and parts synthetic fine s ilica, byweight, by blending in a Waring Blendor. Th'e fine dust is particularlyuseful for application to broadleat plants for the control of aphids.

Although not intending to be limited by a theoretical explanation, theeffectiveness of the compounds of the present invention to controlinsects is attributed to the property of these novel compounds to mimicthe activity of juvenile hormone as demonstrated herein. While themethods of applying and carriers for conventional insecticides areusually adaptable to the practical use of the compounds of the presentinvention, the mechanism of action of these compounds is unlike that ofconventional insecticides. Whereas conventional insecticides aredependent upon direct knock-down efiect, toxity effect or paralyzingeffect, the compounds of this invention achieve control by reason oftheir ability to inhibit metamorphosis, inhibit reproduction due toabnormal development, break diapause at an unfavorable time, or act as adirect insecticide, particularly at the embryo stage and larvae stage.Treatment of insects in accordance with the present invention can beachieved -via ingestion of the active compound in the normal food of theinsect and by topical application, that is-by contact of the epidermisof the insect as by spraying the insect and habitat of the insect orexposure to vapors of the active compound which penetrate into theinsect.

The compounds of the present invention can be used in conjunction withother juvenile hormone active substances and conventional insecticidesto obtain a broad spectrum of activity or to provide more immediateefiect on very heterogeneous populations. Typical insecticides which maybe combined with the compounds of the present invention are Malathion,Sevin, Vapona, Abate, synthetic and natural pyrethrins, and the like,and usually within the ratio of between 10:1 to 1:10, by weight.

EXAMPLE 50 To 3.14 g. of 1l-methoxy-3,7,ll-trimethyldodeca-2,4- dienoicacid in 50 ml. of dry benzene, stirring at room temperature undernitrogen, is added 4.5 ml. (about 4 equivalents) of oxalyl chloride. Thereaction mixture is stirred at room temperature for three hours and thenthe sol-vent is removed under reduced pressure.

To the thus-prepared acid chloride is added 75 ml. of

fresh dry benzene and the mixture is cooled in an icebath. Cyclopropylamine (3.31 ml., about 4 equivalents) in 100 ml. of cold dry benzene isadded to the acid chloride solution. The reaction mixture is allowed tocome to room temperature and then is stirred for five minutes. Most ofthe solvent is removed in vacuo, the concentrate is poured into waterand extracted with ether, and the organic extracts are washed withdilute hydrochloric acid, water and brine, dried over calcium sulfateand evaporated under vacuum to yield N-cyclopropyl ll-methoxy-3,7,11-trimethyldodeca-2,4-dienamide, which can be puri- -fied bychromatography and distillation.

EXAMPLE 1 Following the procedure of Example 41, each of dicyclopropylamine, but-3-yn-l-yl amine, prop-2-yn-1-yl amine (propargyl amine) andcyclobutyl amine is reacted with the acid chloride of11-methoxy-3,7,l1-trimethyldodeca-2,4-dienoic acid to prepare:

N,N-di( cyclopropyl) 1 1-methoxy-3,7, l l-trimethyldodeca-2,4-dienamide,

N- (but-3'-yn- '-yl) 1 1-methoxy-3,7, l l-trimethyldodeca-2,4-dienamide,

N-(prop-2-yn-1'-yl) l 1-methoxy-3,7, 1 l-trimethyldodeca- 2,4-dienamide,and

N-cyclobutyl 1 1-methoxy-3,7,l 1-trimethyldodeca-2,4-

dienamide.

Following the procedure hereinabove, each of N-ethyl l l-methoxy-3,7,l1-trimethyldodeca-Z,4-dienamide (about 73% trans,trans) and N-ethyl11-hydroxy-3,7,1l-trimethy1dodeca-2,4-dienamide (mostly trans,trans) wastested on Tenebrio molitor pupae resulting in an ID of less than 0.001g.

Testing of N-isopropyl 11-met1h0xy-3,7,ll-trimethyldodeca-2,4-dienamide(about 74% trans,trans) on Aedes aegypti according to the proceduredescribed above resulted in an IC of less than 0.1 p.p.m.

By use of an atomizing device, two seedling pea plants nine to elevendays of age are sprayed until run-01f is imminent. Approximately 5 ml.of spray solution are dispensed during this operation. The said spraysolution is prepared by added 1.0 ml. of an acetone solution whichcontains an appropriate, predetermined amount of N-ethyl 11methoxy-3,7,ll-trimethyldodeca 2,4 dienamide (about 73% trans,trans),aqueous 0.01% emulsion of the surfactant Tween 20 [polyoxyethylene (20)sorbitan monolaurate]. A pair of pea plants is also sprayed with a 1 to9 preparation of acetone in 0.01% Tween 20 to serve as spray diluentcontrols. The aqueous sprays on the plants are allowed to dry.Individual plants are then infested with ten third instar larvae of thepea aphid Acyrthosiphon pisum (Harris) which are 72 to 96 hours of agefrom time of birth. The aphids are then encaged by placing a disposablepaperboard cylinder over the pot in which each sprayed and infested peaplant is maintained. The cylinder is closed at the top with fine meshnylon screen to retain aphids which leave the plant. En

caged plant units are transferred to an environmental greenhousemaintained under constant conditions (25 C., 50% relative humidity, 16hours light per day) and held therein for a period of six days. Duringthis time, the said substrate of each pea plant is watered as may benecessary. At the end of this holding period, the aphids on each plantare scored using the following system: 0=a normal adult; l=a moderatelyaffected aphid which exhibits characters intermediate between those ofthe normal adult and the fourth instar larva; and 2=a strongly affectedaphid which exhibits one or more of the following characteristics:evidence of an extra-larval instar(s), inhibited reproduction, genitalpore sclerotized and cauda more larval than adult in shape. For eachplant, the sum of the two products of the number of individuals in eachcategory times the category score is divided by 20 (maximum score) toobtain the percent response. The result from the duplicate assays areaveraged to obtain the percent response for the particular dose levelapplied. Two or more dose levels (stated as percent concentration) areapplied. The I0 level for the compound is then determined from asemi-logarithmic plot of percent response versus the logarithm of thepercent concentration. For N ethyl 11methoxy-3,7,l1-trimethyldodcca-2,4-dienamide, an IC value of less than0.03% was obtained. Controls exhibited negligible (2% or less) responsethroughout the similar series of assays.

Each of N-cyclopropyl 11 methoxy-3,7,11-trimethyldodeca-2,4-dienamide(mostly trans,trans) and N-isopropyl ll-methoxy-3,7,l1-trimethyldodeca2,4 dienamide (mostly trans,trans) was applied to Tenebrio molitor pupaeusing the procedure described hereinabove resulting in ID of less than0.06 pg. and 0.02 ,ug., respectively.

What is claimed is:

1. A compound selected from those of the Formula A:

wherein,

Z is bromo, chloro, fluoro or the group -OR in which R is hydrogen,carboxylic acyl of one to eighteen carbon atoms, lower alkyl,cycloalkyl, aralkyl or aryl;

Z is hydrogen, bromo, chloro or fluoro;

n is zero or the positive integer one;

each of R R R and R is lower alkyl;

each of R R and R is hydrogen or lower alkyl; and

each of R and R is hydrogen, alkyl, lower alkenyl, lower alkynyl,cycloalkyl, hydroxyalkyl, alkoxyalkyl, alkylthiaalkyl, aryl or aralkylor, when taken together with the nitrogen atom to which they areattached, pyrrolidino, morpholino, piperidino, piperazino or4-alkylpiperazino, provided that when Z is 'bromo, chloro or fluoro,then Z is bromo, chloro or fluoro, respectively.

2. A compound according to claim 1 wherein Z' is hydrogen; each of R R Rand R is methyl or ethyl; each of R R and R is hydrogen or methyl; and Zis chloro or the group -OR.

3. A compound according to claim 2 wherein each of R and R is hydrogen;R is methyl; and Z is chloro or the group ()R in which R is hydrogen,methyl, ethyl, isopropyl, t-butyl or acetyl.

4. A compound according to claim 3 wherein R is hydrogen and each of R,R and R is methyl.

5. The trans (2), trans (4) isomer of a compound according to claim 4.

6. A compound selected from those of the formula:

wherein,

Z is bromo, chloro, fiuoro or the group OR in which R is hydrogen,carboxylic acyl of one to eighteen car bon atoms, lower alkyl,cycloalkyl, aralkyl or aryl;

Z is hydrogen, bromo, chloro or fluoro;

n is zero or the positive integer one;

each of R R R and R is lower alkyl;

each of R R and R is hydrogen or lower alkyl; and

each of R and R is hydrogen, lower alkyl, lower alkenyl, lower alkynyl,cycloalkyl, lower hydroxyalkyl, lower alkoxyalkyl, lower alkylthiaalkyl,aryl or aralkyl.

7. A compound according to claim 6 wherein Z is hydrogen; each of R R Rand R is methyl or ethyl; each of R R and R is hydrogen or methyl; and Zis chloro or the group OR.

8. A compound according to claim 7 wherein R is methyl; Z is chloro orthe group OR in which R is hydrogen, methyl, ethyl, isopropyl, t-butylor acetyl; and each of R and R is hydrogen.

9. A compound according to claim 8 wherein each of R R and R is methyl.

10. A compound according to claim 9 wherein R is hydrogen.

11. The trans (2), of claim 10.

12. A compound according to claim 11 wherein Z is chloro or the group ORin which R is hydrogen or methyl and each of R and R is hydrogen orlower alkyl.

13. A compound according to claim 12 wherein Z is the group OR in whichR is methyl and each of R and R is hydrogen, methyl, ethyl or isopropyl.

14. A compound according to claim 13 wherein each of R and R is ethyl.

15. A compound according to claim 13 wherein R is hydrogen and R isethyl or isopropyl.

16. A compound according to claim of R and R is hydrogen or lower alkyl.

17. A compound according to claim 6 wherein'R is methyl; each of R, Rand R is methyl or ethyl; each of R R and R is hydrogen or methyl; Z ishydrogen; Z is chloro or the group OR in which R is hydrogen, methyl,ethyl, isopropyl, t-butyl or acetyl; and n is one.

18. A compound according to claim 17 wherein each of R and R is hydrogenor lower alkyl.

19. A compound according to claim 18 wherein each of R and R ishydrogen; each of R and R is methyl; and Z is chloro or the group OR inwhich R is hydrogen, methyl, ethyl or isopropyl.

20. A compound according to claim 19 wherein each of R and R ishydrogen, methyl, ethyl or isopropyl.

21. A compound according to claim 19 wherein R is hydrogen and R isethyl.

22. The trans (2), trans' (4) isomer of a compound according to claim 21wherein Z is methoxy and R is hydrogen.

trans (4) isomer of a compound 8 wherein each 23. The compound, N-ethyl11-methoxy-3,7,11-trimethyldodeca-Z (trans), 4 (trans)-dienamide,according to claim 22.

24. A compound according to claim 19 wherein each of R and R is ethyl.

25. The trans (2), trans (4) isomer of a compound according to claim 24wherein Z is methoxy and R is hydrogen.

26. The compound, N,N-diethy1 1 1-methoxy-3,7,11-trimethyldodeca-Z-(trans), 4 (trans)-dienamide, according to claim 25.

27. A compound according to claim 19 wherein R is hydrogen and R isisopropyl.

28. The trans (2), trans (4) isomer of a compound according to claim 27wherein Z is methoxy and R is hydrogen.

29. The compound, N-isopropyl 11-methoxy-3,7,1ltrimethyldodeca-Z(trans), 4 (trans)-dienamide, according to claim 28.

30. A compound according to claim 10 wherein Z is chloro or the group ORin which R is hydrogen or methyl; R is hydrogen, cycloalkyl, loweralkenyl or lower alkynyl; and R is cycloalkyl, lower alkenyl or loweralkynyl.

31. A compound according to claim 30 wherein Z is the group OR in whichR is methyl; R is hydrogen; and R is lower alkenyl of two to four carbonatoms.

32. A compound according to claim 30 wherein Z is the group OR in whichR is methyl and each of R and R is lower alkenyl of two to four carbonatoms.

33. A compound according to claim 30 wherein Z is the group OR in whichR is methyl; R is hydrogen; and R is cycloalkyl.

34. A compound according to claim 30 wherein Z is the group OR in whichR is methyl and each of R and R is cycloalkyl.

35. A compound according to claim 30 wherein Z is the group OR in whichR is methyl; R is hydrogen; and R is lower alkynyl of three to fourcarbon atoms.

36. A compound according to claim 30 wherein Z is the group OR in whichR is methyl and each of R and R is lower alkynyl of three to four carbonatoms.

References Cited UNITED STATES PATENTS 5/ 1973 Henrick et al 260-404 X9/1972 Henrick et al. 260404 X LEWIS GO'ITS, Primary Examiner E. G.LOVE, Assistant Examiner UNITED STATES PATENT OFFICE CERTIFICATE OFCORRECTION Patent No. 3 803 ,185 Dated April 9 1974 Inventor(s) Cli veA. Henri ck and John B. Siddall It is certified that error appears inthe above-identified patent and that said Letters Patent are herebycorrected as shown below:

Claim 1 line 51, "each of R and R is hydrogen" should read each of R andR is hydrogen; and

-line 56 to line 57, delete "provided that when Z is bromo, v.respectively."

Signed and sealed this 3rd day of December 1974.

(SEAL) Attest:

McCOY M. GIBSON JR. 0. MARSHALL DANN Attesting Officer Commissioner ofPatents USCOMM-DC 60376-P69 FORM PO-105O (10-69) a u.'S. sovznkncmvmm'me omc: 1 I969 o-zaa-aaa

